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Descriptions of intervention(s) / exposure

Investigational drug: Sativex (1 spray: 2.7 mg THC and 2.5 mg CBD) in an alcohol and peppermint oil liquid administered as an oromucosal spray onto the inside of the mouth (but not intended to be swallowed and digested through the stomach - so some time (1 minute) should be taken after each single spray is administered to ensure absorption, before the next spray is administered). The patient cannot choose when they receive their 8 spray dose, they must have them all at the 6 hourly interval.

Dosage form/strength: maximum 800 uL every six hours (X8 sprays every six hours). Participants may not take partial doses (i.e. 6 sprays) but they can ask to miss up to two of the 6 hourly dose in a day. Patients are in hospital for 8 nights, discharging on day 9.

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Reason:

Intervention Code:

Treatment: drugs2644050

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Reason:

Comparator / control treatment

Placebo spray - comprising alcohol and peppermint oil

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Reason:

Control group

Placebo

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Reason:

Page 4

Primary Outcome:

Self-reported measures of cannabis withdrawal using the Cannabis Withdrawal Scale (a modified version of the MWC (Budney et al., 1999)).2665220

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Reason:

Timepoint:

Four times a day for 9 days (6am, 11 am, 6pm and 10pm)2665220

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Reason:

Primary Outcome:

Treatment completion, defined as completing 9 days of inpatient treatment under protocol conditions (categorical yes/no); and number of days of inpatient treatment completed (range: 0-9).2665230

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Reason:

Timepoint:

Quantified once on day of patient discharge from hospital2665230

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Reason:

Primary Outcome:

Adverse events during the inpatient treatment period using a tailor made Adverse Events Checklist and administered by clinician/nurse/medical officer. Adverse events may include any of the following: Dizziness, Dry mouth, Tachycardia, Stomache ache, Slowed motor skills, slowed reaction time, anxiety, dysphoria, paranoia, oro-mucosal ulceration. Adverse events will be rated on a 0 - 3 scale, 0 being None, 1 being Mild, 2 being Moderate, 3 being Severe.2665240

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Reason:

Timepoint:

Once daily for the 9 days of inpatient stay2665240

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Reason:

Secondary Outcome:

Self-reported cannabis use with total days used cannabis (range 0-28) and longest period of continuous abstinence (range 0-28) during the one month follow-up period (quantifying rates of continuous and point prevalence abstinence from cannabis, time to relapse, levels of cannabis use, and cannabis related problems at follow up), using the Timeline Followback method2739570

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Reason:

Timepoint:

At baseline (day 1 of entry into inpatient unit) for the previous 28 days, and at follow up (28 days after discharge from hospital)2739570

Baseline (Day 1), Discharge (Day 9) and Follow up (28 days after discharge)2739630

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Reason:

Secondary Outcome:

Depression, Anxiety and Stress measures using the 21 item version of the Depression, Anxiety and Stress Scale (Lovibond & Lovibond, 1995)2739640

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Reason:

Timepoint:

Baseline (Day 1), Discharge (Day 9) and Follow up (28 days after discharge)2739640

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Reason:

Secondary Outcome:

Quality of life using the Sheehan Disability Scale2739650

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Reason:

Timepoint:

Baseline (Day 1) and Follow up (28 days after discharge)2739650

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Reason:

Secondary Outcome:

Self efficacy for Quitting Cannabis Questionnaire2739660

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Reason:

Timepoint:

Baseline (Day 1), Discharge (Day 9) and Follow up (28 days after discharge)2739660

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Reason:

Secondary Outcome:

Anxiety Sensitivity Index2739670

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Reason:

Timepoint:

Baseline (Day 1) and Follow up (28 days after discharge)2739670

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Reason:

Secondary Outcome:

Distress tolerance Scale2739680

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Reason:

Timepoint:

Baseline (Day 1) and Follow up (28 days after discharge)2739680

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Reason:

Page 5

Key inclusion criteria

1. Between 18-65 years of age (Both males and females)2. Regular recent cannabis use (average of 5 times per week – self report)3. Meet DSM-IV-TR 'Registered Trademark' criteria for cannabis dependence4. Has made unsuccessful quit attempts in the past 5. Desire to give up cannabis6. Prepared to enter a hospital ward for 9 days

If NO to any (1 - 6) client is not eligible for SATIVEX trial phone screen, provide usual referral/treatment advice.

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Reason:

Minimum age

18Years

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Reason:

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Reason:

Maximum age

65Years

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Reason:

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Reason:

Gender

Both males and females

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Reason:

Healthy volunteers?

No

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Reason:

Key exclusion criteria

1. More than twice weekly use of an illicit drug in the last 30 days (other than cannabis)2. Dependence on a substance other than cannabis and tobacco3. Pregnant or breastfeeding4. Female of child bearing potential NOT using contraception5. Evidence of severe medical impairment (e.g. chronic pain, severe hepatic impairment or cardiovascular disease)6. Evidence of severe cognitive or psychiatric impairment (e.g. bipolar, schizophrenia, suicidal ideation)7. Current (within past month) prescription for antipsychotic or mood stabilising medications 8. Currently prescribed warfarin9. Allergy to cannabinoids, propylene glycol, ethanol or peppermint oil10. Not English literate 11. Specialist substance use treatment in the last 30 days

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Reason:

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Study type

Interventional

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Reason:

Purpose of the study

Treatment

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Allocation to intervention

Randomised controlled trial

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Reason:

Describe the procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation involves contacting the holder of the allocation schedule who was "off-site" or at central administration

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Reason:

Describe the methods used to generate the sequence in which subjects will be randomised (sequence generation)

Permuted block randomisation

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Reason:

Masking / blinding

Blinded (masking used)

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Reason:

Who is / are masked / blinded (choose all that apply)

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Reason:

Assignment

Parallel

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Reason:

Other design features

Participants receive either Sativex or Placebo - never both, and participants are anticipated to come into the study one at a time (at each of the two study sites)

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Reason:

Type of endpoint(s)

Safety/efficacy

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Reason:

Statistical Methods/Analysis

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Reason:

Page 7

Phase

Phase 2

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Reason:

Anticipated date of first participant enrolment

31/07/2011

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Reason:

Date of first participant enrolment

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Reason:

Anticipated date last participant recruited/enrolled

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Reason:

Actual date last participant recruited/enrolled

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Reason:

Target sample size

50

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Reason:

Actual sample size

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Reason:

Recruitment status

Not yet recruiting

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Reason:

Recruitment in Australia

Recruitment state(s)

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Reason:

Postcode:

200039210

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Reason:

Postcode:

230039220

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Reason:

Recruitment outside Australia

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Funding Source:

Government body2648700

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Reason:

Name:

National Health and Medical Research Council2648700

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Reason:

Address:

Level 116 Marcus Clarke StreetCanberra ACT 26012648700

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Reason:

Country:

Australia2648700

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Reason:

Primary Sponsor

University

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Reason:

Name:

University of New South Wales

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Reason:

Address:

The University of New South WalesSYDNEYNSW 2052AUSTRALIA

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Reason:

Country:

Australia

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Reason:

Secondary Sponsor:

None2639710

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Reason:

Name:

2639710

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Reason:

Address:

2639710

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Reason:

Country:

2639710

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Reason:

Other Collaborator:

Hospital2519410

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Reason:

Name:

Belmont District Hospital2519410

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Reason:

Address:

Croudace Bay Road, Belmont NSW 22802519410

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Reason:

Country:

Australia2519410

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Reason:

Other Collaborator:

Hospital2519420

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Reason:

Name:

Sydney & Sydney Eye Hospital2519420

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Reason:

Address:

GPO Box 1614, Sydney NSW 2001 Australia2519420

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Reason:

Country:

Australia2519420

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Reason:

Page 9

Has the study received approval from at least one Ethics Committee?

Yes

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Reason:

Ethics Committee name:

Hunter New England Research Ethics Committee2668310

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Reason:

Address:

Locked Bag No 1New Lambton, NSW 23052668310

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Reason:

Country:

Australia2668310

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Reason:

Approval Date:

02/02/20112668310

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Reason:

Submitted Date:

2668310

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Reason:

HREC:

10/12/15/3.022668310

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Reason:

Brief summary

The primary objective of the study is to examine the safety and efficacy of SATIVEX 'Registered Trademark (R)' in the inpatient management of cannabis withdrawal, in a double blinded randomised trial compared to placebo. Specifically, the study will compare withdrawal severity, detoxification completion and adverse events between the two conditions in an intention-to-treat analysis. Secondary objectives include 1-month post-withdrawal outcomes (including cannabis and other drug use and psychosocial outcomes), and to assess the relationship between the number, severity and duration of cannabis withdrawal symptoms and rates of continuous and point prevalence abstinence from cannabis, time to relapse, levels of cannabis use, and cannabis related problems at one month follow-up. The study will also explore the cognitive impact of withdrawing from cannabis, as well as the impact of SATIVEX on cognitive functioning, with an aim to assessing the real world safety profile of the drug ahead of larger outpatient studies. The study will also explore the pharmacokinetics and metabolites associated with SATIVEX (R) administration to develop a protocol for differentiating between SATIVEX(R) and illicit cannabis in blood or urine among those entering cannabis withdrawal treatment. This pharmacokinetic assay will prove useful for future large scale outpatient trials should the current trial prove successful. A final exploratory objective of the study is to determine whether there is evidence of an interaction with the efficacy of SATIVEX(R) and patient characteristics on admission (including demographics and cannabis and other use and psychosocial factors such as treatment expectancy) on reported severity of cannabis withdrawal and subsequent post-withdrawal outcomes (cannabis use, psychosocial outcomes, sleep disturbances and cannabis-related problems) to be fully tested in a larger community study.